A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Monoclonal Antibody (mAb) in Patients With IPF

Idiopathic Pulmonary Fibrosis Clinical Trial

Official title:

PhIb, Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability, and PK of an i.v. mAb After Single Ascending Doses in Subjects Affected by Idiopathic Pulmonary Fibrosis.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05513950
• Other study ID #: CLI-10067AA1-01
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 25, 2023
• Est. completion date: June 25, 2024

Study information

• Verified date: April 2024
• Source: Chiesi Farmaceutici S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety of CHF10067 (the study drug) and any side effects that might be associated with it. In addition, the study will evaluate how much of the study drug gets into the bloodstream and how long the body takes to remove it. The body's immune response to the study drug will also be evaluated. The study may also evaluate the effect of the study drug on the level of a certain protein in the body.

Chiesi is conducting this study on patients affected by idiopathic pulmonary fibrosis (IPF, a lung disease).

Chiesi is doing this study to establish the doses suitable for future studies.

Description:

The principal aim of this study is to obtain safety and tolerability data when CHF10067 is administered intravenously as single ascending doses to subjects with IPF. This information, together with the pharmacokinetic (PK) and immunogenicity data, will help establish the doses suitable for future studies in subjects. The effect of CHF10067 on TG2 levels will also be investigated as an exploratory endpoint.

A sequential group, single ascending dose design has been chosen for safety reasons because CHF10067 is in the early stages of clinical development and no data in the IPF population has been collected so far. In addition, sentinel dosing will be used so that in each cohort 2 subjects (1 CHF10067 and 1 placebo) will be dosed at least 24 hours before the remaining 6 subjects.

The study will be double-blind and placebo-controlled to avoid bias in the collection and evaluation of data during its conduct. Placebo has been chosen as the comparison treatment to assess whether any observed effects are treatment-related or simply reflect the study conditions.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: June 25, 2024
• Est. primary completion date: June 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Subject's written informed consent obtained prior to any study-related procedure.

• Males or females, of any race, aged = 40 years of age.

• Body weight = 45 kg.

• Diagnosis of IPF as defined by current American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines. Diagnosis of IPF must be within the past 5 years prior to enrolment, and in the opinion of the Investigator, has been stable for at least 3 months.

• Subjects not receiving any IPF treatment (including subjects with previous use of antifibrotic treatment that has been stopped for at least 2 weeks prior to screening) or receiving well-tolerated standard of care approved treatments at a stable dose for at least 8 weeks prior to screening (nintedanib or pirfenidone) and it is anticipated the dose will remain unchanged throughout the study.

• Forced vital capacity (FVC) = 50% of predicted and ratio of forced expiratory volume in the first second (FEV1)/FVC = 0.7 at screening.

• Diffusing capacity of the lung for carbon monoxide (DLCO; corrected for haemoglobin) = 35% at screening.

• Able to understand the study procedures and the risks involved.

• Male and Female subjects following contraceptive requirements detailed in the study protocol.

Exclusion Criteria:

• History of lower respiratory tract infection within 4 weeks prior to screening and up to Day 1 of the study.

• History of acute exacerbation of IPF within 3 months prior to screening and up to Day 1 of the study

• Active diagnosis of lung cancer or a history of lung cancer.

• Active cancer or a history of cancer (other than lung cancer) with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases).

• Infiltrative lung disease other than IPF

• Subjects exhibiting unhealed wounds or foot ulcers or have known history of wound healing complications.

• Chronic heart failure categorized as New York Heart Association Class II, III, or IV; clinical diagnosis of cor pulmonale requiring specific treatment; or severe pulmonary hypertension

• Currently receiving, or have received, a systemic corticosteroid, immunosuppressant, cytotoxic therapy, vasodilator therapy for pulmonary hypertension, or unapproved or investigational treatment for IPF within 4 weeks prior to screening or prior to randomization.

• Coronavirus disease-2019 (COVID-19) vaccine at least 7 days before dosing. Any systemic symptoms (e.g. myalgia, fever, chills, fatigue, etc.) after COVID-19 vaccine should subside at least 2 days before the Day 1 visit.

• Documented COVID-19 diagnosis within the last 4 weeks or which has not resolved within 7 days prior to screening or before treatment.

• Known intolerance and/or hypersensitivity to any of the excipients contained in the formulation or any other substance used in the study.

• History of allergic or anaphylactic reaction to human, humanised, chimeric, immunoglobulins (Igs), or murine monoclonal antibodies.

• Clinically relevant abnormal laboratory values (clinical chemistry and haematology) at screening suggesting an unknown disease and requiring further clinical investigation or which may impact the safety of the subject or the evaluation of the study results according to Investigator judgement. .

• Pregnant or lactating women.

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Biological:
• CHF10067 starting dose
Intravenous administration of a starting dose of the monoclonal antibody
• CHF10067 intermediate dose
Intravenous administration of an intermediate dose of the monoclonal antibody
• CHF10067 high dose
Intravenous administration of a high dose of the monoclonal antibody

Drug:
• Placebo
Intravenous administration of a physiological solution as placebo.

Locations

Country	Name	City	State
North Macedonia	PHI University Clinic of Pulmonology and Allergology	Skopje
Ukraine	Medical Center of Limited Liability Company "Arensia Exploratory Medicine", department of Clinical Trials	Kyiv
United Kingdom	Queen Elizabeth Hospital - NIHR Birmingham Clinical Research Facility - University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Royal Papworth Hospital NHSFT - Cambridge Biomedical Campus	Cambridge
United Kingdom	University of Dundee, NHS Tayside - Ninewells Hospital & Medical School	Dundee
United Kingdom	Interstitial Lung Disease Research - NHS Lothian - Royal Infirmary of Edinburgh,	Edinburgh
United Kingdom	Liverpool Clinical Research Facility - Liverpool University Hospital Foundation Trust	Liverpool
United Kingdom	Medicines Evaluation Unit - The Langley Building	Manchester
United Kingdom	University Hospital Southampton - Department of Respiratory Medicine	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
Chiesi Farmaceutici S.p.A.

Countries where clinical trial is conducted

North Macedonia,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Transglutaminase 2 levels in plasma	To evaluate Transglutaminase 2 levels in plasma changes from baseline over time will be described	From predose up to 84 days post dose
Primary	Adverse Event recording	Adverse Event recording	From pre-dose up to day 84
Secondary	Systemic exposure (area under the concentration-time curve from zero to time) to CHF10067.	To evaluate the area under the concentration-time curve from zero to the last quantifiable concentration (AUC0-t) of CHF10067 after a single dose.	From pre-dose up to day 84
Secondary	Area under the concentration-time curve from zero to infinity (AUC0-8) of CHF10067	To evaluate the area under the concentration-time curve from zero to infinity (AUC0-8) of CHF10067 after a single dose	From pre-dose up to day 84
Secondary	Maximum plasma concentration (Cmax) of CHF10067	To evaluate the Cmax (maximum observed concentration) after a single dose of CHF10067	From pre-dose up to day 84
Secondary	Time to Cmax	To evaluate the Time to Cmax (tmax) (time to maximum observed concentration)	From pre-dose up to day 84
Secondary	terminal half-life (t1/2) of CHF10067	To evaluate the Time to t1/2 of CHF10067	From pre-dose up to day 84
Secondary	Evaluation of CHF10067 immunogenicity profile	Evaluation of Anti Drug Antibodies and neutralising antibody (nAb)	From predose up to 84 days post dose
Secondary	Vital signs	Systolic and diastolic blood pressure	From pre-dose up to day 84
Secondary	Oxygen saturation	Oxygen saturation measured via pulse oximetry	From pre-dose up to day 84
Secondary	12-lead ECG (Electrocardiogram) - HR	The Heart Rate will be summarised using descriptive statistics at each analysis time point by treatment.	From pre-dose up to day 84
Secondary	12-lead ECG (Electrocardiogram)-PR interval	PR interval will be summarised using descriptive statistics at each analysis time point by treatment.	From pre-dose up to day 84
Secondary	12-lead ECG (Electrocardiogram) - QRS interval	QRS Interval will be summarised using descriptive statistics at each analysis time point by treatment.	From pre-dose up to day 84
Secondary	12-lead ECG (Electrocardiogram) QTCF	the number and percentage of subjects with abnormal actual QTCF (QT corrected for heart rate by Fridericia's formula)	From pre-dose up to day 84
Secondary	Spirometry FEV1	FEV1 (forced expiratory volume in the first second) parameters will be summarised using descriptive statistics at each analysis time point by treatment.	From pre-dose up to day 84
Secondary	Spirometry FVC	FVC (forced vital capacity) parameters will be summarised using descriptive statistics at each analysis time point by treatment.	From pre-dose up to day 84
Secondary	Diffusing capacity (DLCO)	Diffusing capacity (DLCO) parameters will be summarised using descriptive statistics at each analysis time point by treatment.	From pre-dose up to day 84
Secondary	Body temperature	Body temperature will be monitored	at screening, pre-dose, every 15 minutes during the infusion (e.g., 15, 30, 45, 60, 75, 90, 105, etc.), at the end of the infusion and 30 min, 1, 2, 3, 4, 6, 8, and 20 hours after the end of the infusion and 5, 7, 14, 28, 56, and 84 days post-dose
Secondary	Pulse rate	Pulse rate will be monitored	At screening, pre-dose, every 15 minutes during the infusion (e.g., 15, 30, 45, 60, 75, 90, 105, etc.), at the end of the infusion and 30 min, 1, 2, 3, 4, 6, 8, and 20 hours after the end of the infusion and 5, 7, 14, 28, 56, and 84 days post-dose
Secondary	Respiratory rate	Respiratory rate will be monitored	At screening, pre-dose, every 15 minutes during the infusion (e.g., 15, 30, 45, 60, 75, 90, 105, etc.), at the end of the infusion and 30 min, 1, 2, 3, 4, 6, 8, and 20 hours after the end of the infusion and 5, 7, 14, 28, 56, and 84 days post-dose